With the advance of the Human Genome Program, a strong movement has been under way to understand living bodies on the DNA level, and thereby to understand the tests of diseases and life phenomena. Investigation on the expression profiles of genes is effective for understanding life phenomena and investigating the actions of genes. As an effective method for investigating the gene expression profile, a DNA probe array obtained by immobilizing a large number of DNA probes in groups divided according to the kinds thereof on the surface of a solid such as slide glass, or a DNA chip, or further a protein chip has come into use.
Examples of a technology for fabricating such a chip include: a method in which an oligomer with a designed sequence is synthesized base by base in each of a large number of cells sectioned on a slide glass by using a lithography technology to be widely used in a photochemical reaction and the semiconductor industry (Science 251, 767–773 (1991); and a method in which a plurality of kinds of DNA probes are spotted one by one to each segment (Anal. Chem. 69, 543–551 (1997), Nat. Biotechnol., 18, 438–441 (2000)).
On the other hand, another method is proposed, wherein micro-particles having DNA probes immobilized thereto are prepared, and a plurality of kinds of such micro-particles are collected, thereby to fabricate a probe array (Clinical Chemistry 43, 1749–1756 (1997), Nucleic Acids Research Supplement No. 1, 83–84 (2001)). Use of micro-particles has an advantage in that a probe array having no variation in probe density between micro-particles can be fabricated because a probe immobilizing method utilizing chemical reactions in a solution is usable.
For the probe array on a slide glass, the following method is adopted. Namely, the probe species is identified according to the oligomer formation position or the spot position of each DNA probe or protein probe. As for the probe array using probe conjugated micro-particles, there is adopted a method in which micro-particles color coded for respective probes are used (Clinical Chemistry 43, 1749–1756 (1997)), or a method in which the probe species is identified according to the arraying order of the micro-particles in a capillary (Nucleic Acids Research Supplement No. 1, 83–84 (2001)).
In the prior art, any method of fabrication of a DNA probe array or a DNA chip requires the immobilization of DNA probes or synthesis of oligomers base by base for every array. Therefore, the fabrication requires much time and trouble, resulting in a high fabrication cost. Further, the probes are immobilized each in droplet form on the solid surface. This presents the following deficiencies: for example, the probes vary from one section to another section; the combination of probe species is not easy to change; and a user cannot operate them with ease.
In order to solve the foregoing problems, there was proposed a probe array using micro-particles, i.e., micro-particle array, obtained by separate steps of immobilizing probes on the solid surfaces and arraying the probes (Nucleic Acids Research Supplement No. 1, 83–84 (2001)). In order to achieve practical utilization of the micro-particle array, and to sell the micro-particle array positioned in a capillary or a chip at a low price, it is essential to establish apparatus and method for selecting given probe-immobilized micro-particles according to the test purpose, and arraying the micro-particles as desired.
Heretofore, as this technology, the following methods have been proposed: a method in which micro-particles are poured into a capillary utilizing the flow of a liquid on a one-by-one basis under control (Japanese Laid-Open Patent Publication No. Hei 11-243997); and a method in which only one micro-particle out of a plurality of micro-particles introduced together with a solvent is held on a sheet provided with a micro-hole capable of receiving only one micro-particle, and the sheet holding the micro-particle is moved to a position of a capillary or a channel provided in a flat plate for arrangement (Japanese Laid-Open Patent Publication No. 2000-346842) However, with these methods, the micro-particles may not be efficiently captured under the influence of bubbles, resulting in inferior reliability and operability.
Thus, the apparatus for arraying micro-particles as desired, and a method thereof are yet to be established. It is therefore an object of the present invention to provide novel method and technology for establishment thereof.